title: The cell-penetrating peptide, Pep-1, has activity against intracellular chlamydial growth but not extracellular forms of Chlamydia trachomatis.
abstract: OBJECTIVE
  In the course of studies to identify novel treatment strategies against the pathogenic bacterium, Chlamydia, we tested the carrier peptide, Pep-1, for activity against an intracellular infection.
  
  
  METHODS
  Using a cell culture model of Chlamydia trachomatis infection, the effect of Pep-1 was measured by incubating the peptide with extracellular chlamydiae prior to infection, or by adding Pep-1 to the medium at varying times after infection, and assaying for inhibition of inclusion formation.
  
  
  RESULTS
  Pep-1 had a concentration-dependent effect on chlamydial growth with 100% inhibition of inclusion formation at 8 mg/L peptide. There was a window of susceptibility during the chlamydial developmental cycle with a maximal effect when treatment was begun within 12 h of infection. Pep-1 treatment caused a severe reduction in the production of infectious progeny even when started later, when the effect on inclusion formation was minimal. Furthermore, electron micrographs showed a paucity of progeny elementary bodies (EBs) in the inclusion. In contrast, pre-incubation of EBs with Pep-1 prior to infection did not affect inclusion formation. Taken together, these findings indicate that the antichlamydial effect was specific for the intracellular stage of chlamydial infection. By comparison, Pep-1 had no antimicrobial activity against Escherichia coli and Staphylococcus aureus or the obligate intracellular parasite, Toxoplasma gondii.
  
  
  CONCLUSIONS
  Pep-1 has antichlamydial activity by preventing intracellular chlamydial growth and replication but has no effect on extracellular chlamydiae.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA.
authors.forename: Narae
authors.initials: N
authors.lastname: Park
authors.forename: Kinrin
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Dat
authors.initials: D
authors.lastname: Tran
authors.forename: Pete
authors.initials: P
authors.lastname: Chandrangsu
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Akers
authors.forename: Jessica C
authors.initials: JC
authors.lastname: de Leon
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Morrissette
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000187:drug effects*; D015169:Colony Count, Microbial; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003593:Cytoplasm / Q000648:ultrastructure; D004926:Escherichia coli / Q000187:drug effects; D002479:Inclusion Bodies / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D014122:Toxoplasma / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; C503924:Pep-1 peptide; D010455:Peptides; D003543:Cysteamine